Phase III Trial to Assess Efficacy and Safety of Cetuximab for the Treatment of Chinese Participants With Head and Neck Cancer (CHANGE2)

• ClinicalTrials.gov Identifier: NCT02383966
• Recruitment Status: Completed
• First Posted: March 10, 2015
• Results First Posted: April 16, 2019
• Last Update Posted: May 13, 2022
• Sponsor: Merck KGaA, Darmstadt, Germany
• Information provided by (Responsible Party): Merck KGaA, Darmstadt, Germany

Tracking Information

• First Submitted Date: March 4, 2015
• First Posted Date: March 10, 2015
• Results First Submitted Date: January 18, 2019
• Results First Posted Date: April 16, 2019
• Last Update Posted Date: May 13, 2022
• Actual Study Start Date: July 31, 2015
• Actual Primary Completion Date: January 19, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 18, 2019)

Progression-free Survival (PFS) Time, as Assessed by an Independent Review Committee (IRC) [ Time Frame: Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days) ]

PFS time was defined as the time in months from the date of randomization until first observation of PD (based on imaging as assessed by IRC), or death due to any cause when death occurs within 60 days after the last tumor assessment or randomization (whichever is later). PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on trial; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 millimeter. PFS was measured using Kaplan-Meier (KM) estimates.

Original Primary Outcome Measures (submitted: March 4, 2015)

Progression-free survival (PFS) time, as assessed by an Independent Review Committee (IRC) [ Time Frame: Every 6 weeks (± 3 days) starting from the first dose of trial treatment until occurrence of PD, assessed up to 60 days after the last tumor assessment ]

The duration from the first dose of trial treatment until first observation of progressive disease (PD) (as assessed by an IRC), or death due to any cause when death occurs within 60 days after the last tumor assessment or the first dose of trial treatment (whichever is later). PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on trial; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions.

Current Secondary Outcome Measures (submitted: January 18, 2019)

• Progression-free Survival (PFS) Time, as Assessed by the Investigator [ Time Frame: Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days) ]
  PFS time was defined as the time in months from the date of randomization until first observation of PD (radiologically confirmed by Investigator), or death due to any cause when death occurs within 60 days after the last tumor assessment or randomization (whichever is later). PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on trial; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 millimeter. PFS was measured using Kaplan-Meier (KM) estimates.
• Overall Survival (OS) Time [ Time Frame: Time from date of randomization up to data cutoff (assessed up to 904 days) ]
  The OS time was defined as the time from randomization to the date of death. If a participant was alive at the time of analysis, survival time was censored at the last date when the participant was known to be alive. If this date was after data cut-off, participants were censored at the date of data cut-off. OS was measured using Kaplan-Meier (KM) estimates.
• Best Overall Response Rate (ORR) [ Time Frame: Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days) ]
  The Best ORR was based on imaging and classified according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria. The BOR rate was defined as the number of participants whose BOR was either complete response (CR) or partial response (PR), relative to the number of participants belonging to the trial set of interest. CR was defined as disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
• Disease Control Rate (DCR) [ Time Frame: Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days) ]
  The DCR was based on imaging and classified according to RECIST Version 1.1 criteria. The DCR was defined as the number of participants whose Best Overall Response is either CR, PR or stable disease (SD), divided by the number of participants belonging to the trial set of interest multiplied by 100. CR was defined as disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on trial.
• Duration of Response (DOR) [ Time Frame: Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days) ]
  DOR was determined for participants whose BOR was either CR or PR. It was defined as the time from the first assessment of CR or PR until the event defining PFS time. PFS time was defined as the time in months from the date of randomization until first observation of PD (based on imaging as assessed by IRC), or death due to any cause when death occurs within 60 days after the last tumor assessment or randomization (whichever is later). CR was defined as disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
• Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Treatment Emergent Adverse Events Leading to Death and AEs Leading to Discontinuation [ Time Frame: Time from date of randomization up to data cutoff (assessed up to 904 days) ]
  An Adverse event (AE) was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state up to 30 days after last administration. TEAEs included both Serious TEAEs and non-serious TEAEs.

Original Secondary Outcome Measures (submitted: March 4, 2015)

• PFS time, as assessed by the Investigator [ Time Frame: Every 6 weeks (± 3 days) starting from the first dose of trial treatment until occurrence of PD, assessed up to 60 days after the last tumor assessment ]
  The duration from the first dose of trial treatment until first observation of radiologically confirmed PD (as assessed by the Investigator), or death due to any cause when death occurs within 60 days after the last tumor assessment or the first dose of trial treatment (whichever is later).
• Overall survival (OS) time [ Time Frame: First dose of trial treatment to the date of death, assessed up to 12 months after the last subject randomized ]
  The time from the date of the first dose of trial treatment to the date of death, or last date known to be alive.
• Best overall response (BOR) rate [ Time Frame: Every 6 weeks until occurrence of PD, assessed up to 60 days after the last tumor assessment ]
  The BOR will be based on imaging and classified according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria. The BOR rate is defined as the number of subjects whose BOR was either complete response (CR) or partial response (PR), relative to the number of subjects belonging to the trial set of interest. CR is defined as disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters without unequivocal worsening of non-target lesions, or detection of new lesions.
• Disease control rate (DCR) [ Time Frame: Every 6 weeks until occurrence of PD, assessed up to 60 days after the last tumor assessment ]
  The DCR will be based on imaging and classified according to RECIST Version 1.1 criteria. The DCR is defined as the number of subjects whose BOR is either CR, PR or stable disease (SD), divided by the number of subjects belonging to the trial set of interest. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on trial.
• Duration of response [ Time Frame: Every 6 weeks until occurrence of PD, assessed up to 60 days after the last tumor assessment ]
  Duration of response will be determined for subjects whose BOR was either CR or PR. It is defined as the time from the first assessment of CR or PR until the event defining PFS time.
• Number of Participants With Adverse Events (AEs), Serious AEs, AEs Leading to Death and AEs Leading to Discontinuation [ Time Frame: First dose of trial treatment until 30 days after the last dose of trial treatment ]
  An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase III Trial to Assess Efficacy and Safety of Cetuximab for the Treatment of Chinese Participants With Head and Neck Cancer
• Official Title: A Multicenter, Randomized, Open-label, Phase III Trial to Assess Efficacy and Safety of Cetuximab When Given in Combination With Cisplatin Plus 5 Fluorouracil Versus Cisplatin Plus 5-fluorouracil Alone for the First-line Treatment of Chinese Subjects With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck
• Brief Summary: This trial aimed to assess efficacy and safety of cetuximab when given in combination with chemotherapy compared with chemotherapy alone in Chinese participants with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) as the first-line treatment.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Carcinoma, Squamous Cell of Head and Neck

Intervention

• Drug: Cetuximab
  Participants received Cetuximab as an intravenous infusion at an initial dose of 400 milligrams per square meter (mg/m^2) on Day 1 and a subsequent dose of 250 mg/m^2 on Day 8 and Day 15 of each 21-day treatment cycle.
  Other Name: Erbitux
• Drug: Cisplatin/Carboplatin
  Cisplatin or Carboplatin (at an equivalent dose in case of intolerability of cisplatin) was administered at a dose of 75 mg/m^2 as an intravenous infusion on Day 1 of each 21-day treatment cycle.
• Drug: 5-fluorouracil
  Participants received 5-fluorouracil (FU) at a dose of 750 mg/m^2/day as a continuous intravenous infusion over 24 hours a day from Day 1 to Day 5 of each 21-day treatment cycle.
  Other Name: 5-FU

Study Arms

• Experimental: Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil
  Interventions:

  • Drug: Cetuximab
  • Drug: Cisplatin/Carboplatin
  • Drug: 5-fluorouracil
• Active Comparator: Cisplatin/Carboplatin + 5-Flurouracil
  Interventions:

  • Drug: Cisplatin/Carboplatin
  • Drug: 5-fluorouracil

• Publications *: Guo Y, Luo Y, Zhang Q, Huang X, Li Z, Shen L, Feng J, Sun Y, Yang K, Ge M, Zhu X, Wang L, Liu Y, He X, Bai C, Xue K, Zeng Y, Chang X, Chen W, Lin T. First-line treatment with chemotherapy plus cetuximab in Chinese patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: Efficacy and safety results of the randomised, phase III CHANGE-2 trial. Eur J Cancer. 2021 Oct;156:35-45. doi: 10.1016/j.ejca.2021.06.039. Epub 2021 Aug 18.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 18, 2017): 243
• Original Estimated Enrollment (submitted: March 4, 2015): 240
• Actual Study Completion Date: December 20, 2021
• Actual Primary Completion Date: January 19, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of SCCHN
• Recurrent and/or metastatic SCCHN, not suitable for local-regional treatment
• Presence of at least 1 measurable lesion according to RECIST Version 1.1
• Signed written informed consent before any trial-related activities are carried out
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Other protocol-defined inclusion criteria could apply

Exclusion Criteria:

• Prior systemic chemotherapy, except if given as part of multimodal treatment for locally advanced disease, that was completed within 6 months before randomization
• Surgery (excluding prior biopsy for diagnosis) or irradiation within 4 weeks before trial entry
• Previous treatment with monoclonal antibody or signal transduction inhibitors targeting epidermal growth factor receptor
• Nasopharyngeal carcinoma
• Known central nervous system metastasis and/or leptomeningeal disease
• Medical or psychological condition that would not permit the participant to complete the trial or sign informed consent
• Legal incapacity or limited legal capacity
• Other protocol-defined exclusion criteria could apply

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT02383966
• Other Study ID Numbers: EMR062202-060
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Merck KGaA, Darmstadt, Germany
• Original Responsible Party: Same as current
• Current Study Sponsor: Merck KGaA, Darmstadt, Germany
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Responsible; Merck KGaA, Darmstadt, Germany

• PRS Account: Merck KGaA, Darmstadt, Germany
• Verification Date: April 2022